Nucleotide sequence of the IN genes of leukemogenic mink cell focus-forming murine leukemia virus (L-MCF13 MuLV) and non-leukemogenic (NL) MCF111A MuLV was determined. The two IN genes were diverged in their 51 sequences, whereas the 31 portion was fairly conserved. The biological activity of MCF13 and MCF111A IN genes was studies using an in vitro constructed recombinant MCF13 DNA which contained MCF111A IN gene. The recombinant virus and parental viruses were compared in their leukemogenic potential and ratios of unintegrated and integrated proviral DNAs. The results indicated that the two MuLV IN genes were different in integrase activity. Nucleotide sequence of the IN gene of an endogenous MCF MuLV-related DNA (B34) was determined. The gene was 1230 bp and could potentially encode for a functional protein. Comparative sequence analysis indicated that the endogenous IN gene had 82% sequence homology and 86% amino acid homology with AKV ecotropic MuLV IN. In situ hybridization analysis indicated that human endogenous 4-1 retroviral-related RNAs were expressed at high levels in both human brain and kidney tissues, but only in a few cells.